Parker Waichman LLP Injury Alerts
One Very Dangerous Drug: The Duragesic (Fentanyl) Pain PatchMay 1, 2008
PARKER WAICHMAN NEWSLETTER – MAY 2008
One Very Dangerous Drug: The Duragesic (Fentanyl) Pain Patch
Fentanyl is a drug that is not to be taken lightly. Although prescription and over-the-counter (OTC) painkillers have become commonplace, and are taken by tens of millions of Americans for every imaginable (and even imaginary) kind of pain, often without a second thought, at 80 times the potency of morphine, fentanyl is extremely dangerous and potentially lethal when improper amounts of the drug are dispensed.
Unlike drugs that are taken orally (in liquid or pill form) or by measured injection, fentanyl is released through the skin in a steady dose over an extended period by means of an adhesive patch. As a result, a great deal of trust must be placed in the ability of each patch to work perfectly. Anything short of that can cause the user to quickly suffer extreme distress or death. In fact, at least one medical examiner has stated that a lethal dose of fentanyl can occur so swiftly there may not even be time to call for emergency medical assistance.
Since each patch contains considerably more fentanyl than any patient can safely take in a short period of time, a damaged patch or one that has a cut in it can pose a serious health risk to the user. Moreover, a manufacturing defect in any one patch or in an entire lot of patches may not even be detected until it is too late.
Over the course of the past 14 years, the Duragesic Fentanyl Patch, which is also referred to as the Fentanyl Transdermal System, had been recalled five times. In July 2005, the fifth recall followed the death of 120 patch users.
Fentanyl patches now come in a variety of dosages (indicated by mcg/hr or micrograms per hour) including, 25 mcg/hr, 50 mcg/hr, 75 mcg/hr, and 100 mcg/hr. Clearly, one of the first potential dangers associated with these patches is the possibility of errors involving the dosage. A 100 mcg/hr patch is four times the dosage per hour of a 25 mcg/hr patch. Thus, confusing the two can have deadly effects.
Another problem associated with these patches is their misuse by patients who hold onto unused patches and then give them to other people experiencing pain as if they are nothing more that OTC painkillers like aspirin, Tylenol, Bufferin, or Advil. In May of this year, a six-year-old girl reportedly died after being given a Duragesic patch for her neck pain.
In 2008, however, there have already been multiple recalls of various fentanyl patches manufactured by a number of companies. In February, Johnson & Johnson’s Ortho-McNeil-Janssen unit recalled all lots of its 25 mcg/hr Duragesic pain patch. Shortly thereafter, in March, Actavis issued an expanded recall that included all of its fentanyl patches sold in the United States (25, 50, 75, and 100 mcg/hr). Immediately thereafter, the PriCara Division of Ortho-McNeil-Janssen issued a voluntary recall of all of its 25 mcg/hr Duragesic CII patches sold by PriCara in the U.S. and all 25 mcg/hr fentanyl patches sold by Sandoz Inc. in the U.S. as a precaution.
The problem being encountered with all of these patches is the possibility that leakage, caused by manufacturing defects, may lead to overdosing with fentanyl.
The February 12, 2008, FDA Press Release contained the following information:
PRICARA™ RECALLS 25 mcg/hr DURAGESIC® (fentanyl transdermal system) CII PAIN PATCHES
FOR IMMEDIATE RELEASE -- Raritan, NJ – February 12, 2008 – PriCara, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. said today that all lots of 25 microgram/hour (mcg/hr) DURAGESIC® (fentanyl transdermal system) CII patches sold by PriCara in the United States and all 25 mcg/hr fentanyl patches sold by Sandoz Inc. in the United States are being voluntarily recalled as a precaution from wholesalers and pharmacies. The recalled patches all have expiration dates on or before December 2009, and all are manufactured by ALZA Corporation, an affiliate of PriCara. The recall is being conducted in cooperation with the U.S. Food and Drug Administration. All 25 mcg/hr fentanyl patches manufactured by ALZA and sold in Canada also are being recalled.
DURAGESIC 25 mcg/hr (fentanyl transdermal system) and Sandoz Inc. 25 mcg/hr fentanyl transdermal system patches being recalled may have a cut along one side of the drug reservoir within the patch. The result is possible release of fentanyl gel from the gel reservoir into the pouch in which the patch is packaged, exposing patients or caregivers directly to fentanyl gel. As per the approved product labeling for DURAGESIC, fentanyl is a potent Schedule II opioid medication. Fentanyl patches that are cut or damaged in any way should not be used. Exposure to fentanyl gel may lead to serious adverse events, including respiratory depression and possible overdose, which may be fatal. Anyone who comes in contact with fentanyl gel should thoroughly rinse exposed skin with large amounts of water only; do not use soap. Immediately dispose of affected patches with cut edges by flushing them down the toilet, using caution not to handle them directly. Patches with a cut edge that have leaked gel will not provide effective pain relief.
Anyone who has 25 mcg/hr DURAGESIC or Sandoz Inc. fentanyl patches should check the box or foil pouch for the expiration date to see if they have patches that are being recalled. The recalled patches all have expiration dates on or before December 2009. The cut edge in affected patches can be seen upon opening the sealed foil pouch that holds the patch. Affected patches should not be handled directly.
Anyone with 25 mcg/hr DURAGESIC patches being recalled should call 800-547-6446.
Anyone with 25 mcg/hr Sandoz Inc. patches being recalled should call 800-901-7236.
Patients using fentanyl patches who have medical questions should contact their health-care providers.
For more information, visit www.DURAGESIC. com.
DURAGESIC is used to manage persistent moderate to severe chronic pain that needs to be treated around the clock and which cannot be treated by: combination narcotic, short-acting, or non-narcotic pain treatment products. It should only be used by people who are receiving or have developed a tolerance to pain therapy with opioids. DURAGESIC should not be used if patients have pain that will go away in a few days, such as pain from surgery, medical or dental procedures, or short-lasting conditions. Any adverse reactions experienced with the use of fentanyl patches should be reported to the appropriate company using the telephone numbers above. DURAGESIC brand and other fentanyl patches are available by prescription only, through pharmacies, and should be used only under the supervision of a physician.
DURAGESIC™ patches sold in Europe, Latin America and Asia are not affected by this recall.
The FDA BLACK BOX WARNING reads as follows:
DURAGESIC® contains a high concentration of a potent Schedule II opioid agonist, fentanyl. Schedule II opioid substances which include fentanyl, hydromorphone, methadone, morphine, oxycodone, and oxymorphone have the highest potential for abuse and associated risk of fatal overdose due to respiratory depression. Fentanyl can be abused and is subject to criminal diversion. The high content of fentanyl in the patches (DURAGESIC®) may be a particular target for abuse and diversion.
DURAGESIC® is indicated for management of persistent, moderate to severe chronic pain that:
requires continuous, around-the-clock opioid administration for an extended period of time, and
cannot be managed by other means such as non-steroidal analgesics, opioid combination products, or immediate-release opioids
DURAGESIC® should ONLY be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to DURAGESIC 25 mcg/h. Patients who are considered opioid-tolerant, are those who have been taking, for a week or longer, at least 60 mg of morphine daily, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid.
Because serious or life-threatening hypoventilation could occur, DURAGESIC® (fentanyl transdermal system) is contraindicated:
in patients who are not opioid-tolerant
in the management of acute pain or in patients who require opioid analgesia for a short period of time
in the management of post-operative pain, including use after out-patient or day surgeries (e.g., tonsillectomies)
in the management of mild pain
in the management of intermittent pain [e.g., use on an as needed basis (prn)]
(See CONTRAINDICATIONS for further information.)
Since the peak fentanyl levels occur between 24 and 72 hours of treatment, prescribers should be aware that serious or life threatening hypoventilation may occur, even in opioid tolerant patients, during the initial application period.
The concomitant use of DURAGESIC® with potent cytochrome P450 3A4 inhibitors (ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, and nefazodone) may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Patients receiving DURAGESIC® and potent CYP3A4 inhibitors should be carefully monitored for an extended period of time and dosage adjustments should be made if warranted. (See CLINICAL PHARMACOLOGY – Drug Interactions, WARNINGS, PRECAUTIONS and DOSAGE AND ADMINISTRATION for further information.)
The safety of DURAGESIC® has not been established in children under 2 years of age.
DURAGESIC® should be administered to children only if they are opioid-tolerant and 2 years of age or older (see PRECAUTIONS - Pediatric Use).
DURAGESIC is ONLY for use in patients who are already tolerant to opioid therapy of comparable potency. Use in non-opioid tolerant patients may lead to fatal respiratory depression. Overestimating the DURAGESIC® dose when converting patients from another opioid medication can result in fatal overdose with the first dose. Due to the mean elimination half-life of 17 hours of DURAGESIC®, patients who are thought to have had a serious adverse event, including overdose, will require monitoring and treatment for at least 24 hours.
DURAGESIC® can be abused in a manner similar to other opioid agonists, legal or illicit. This risk should be considered when administering, prescribing, or dispensing DURAGESIC® in situations where the healthcare professional is concerned about increased risk of misuse, abuse or diversion.
Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Patients should be assessed for their clinical risks for opioid abuse or addiction prior to being prescribed opioids. All patients receiving opioids should be routinely monitored for signs of misuse, abuse and addiction. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations; however, these patients will require intensive monitoring for signs of misuse, abuse, or addiction.
DURAGESIC® patches are intended for transdermal use (on intact skin) only. Using damaged or cut DURAGESIC® patches can lead to the rapid release of the contents of the DURAGESIC® patch and absorption of a potentially fatal dose of fentanyl.
On December 21, 2007, the FDA issued the following Public Health Advisory:
FDA Public Health Advisory
Safety Warnings Regarding Use of Fentanyl Transdermal (Skin) Patches
For an updated Public Health Advisory on Fentanyl, please see http://www.fda.gov/cder/drug/advisory/fentanyl_2007.htm
FDA is investigating reports of death and other serious side effects from overdoses of fentanyl in patients using fentanyl transdermal (skin) patches for pain control. Deaths and overdoses have occurred in patients using both the brand name product Duragesic and the generic product. The directions for using the fentanyl skin patch must be followed exactly to prevent death or other serious side effects from overdosing with fentanyl. These directions are provided in the product label and patient package insert.
Some patients and health care providers may not be fully aware of the dangers of this very strong narcotic painkiller. Therefore, FDA is issuing this public health advisory to alert patients and their caregivers and health care professionals by highlighting the following important safety information:
• Fentanyl skin patches are very strong narcotic (opioid) painkillers that may cause death from overdose. The fentanyl skin patch should always be prescribed at the lowest dose needed for pain relief.
• Fentanyl skin patches should not be used to treat short-term pain, pain that is not constant, or for pain after an operation. Fentanyl skin patches should only be used by patients who are already taking other narcotic painkillers (opioid tolerant), and who have chronic pain that is not well controlled with shorter-acting painkillers.
• Patients who are using the fentanyl skin patch and their caregivers should be told about the directions for safe use of the patch and should follow the directions exactly. These directions are provided in the patient package insert
• Patients who are using the fentanyl skin patch and their caregivers should be told about safe methods for storage and disposal of used, unneeded or defective fentanyl skin patches. Fentanyl skin patches should be stored in a safe place and kept out of the reach of children. Safely dispose of used, unneeded or defective fentanyl skin patches by folding the sticky side of the patch together (until it sticks to itself) and flushing it down the toilet.
• Health care professionals who prescribe the fentanyl skin patch and patients who use the fentanyl skin patch and their caregivers should be aware of the signs of fentanyl overdose. Signs of fentanyl overdose include trouble breathing or shallow breathing; tiredness, extreme sleepiness or sedation; inability to think, talk or walk normally; and feeling faint, dizzy or confused. If these signs occur, patients or their caregivers should get medical attention right away.
• A patient using the fentanyl skin patch may have a sudden and possible dangerous rise in their body level of fentanyl or have a stronger effect from fentanyl if they: use other medicines that affect brain function; drink alcohol (beer, wine or distilled spirits); have an increase in body temperature or are exposed to heat; or use other medicines that affect how fentanyl is broken down in the body. These factors are described further in the product label.
In June 2005 the Duragesic product label was updated to add new safety information in several areas of labeling, and a “Dear Healthcare Professional” letter about these changes was issued by the manufacturer and is available at this link (http://www.fda.gov/medwatch/SAFETY/2005/duragesic_ddl.pdf). FDA continues to work with the manufacturers of these products to identify and manage factors that contribute to fentanyl overdose from use of the fentanyl skin patch. Updates will be provided as new information is available.
Finally, we would advise our readers to look over the following excerpts from the Drug Profile from Worst Pills, Best Pills, which is published by the public watchdog organization, Public Citizen:
Generic drug name: fentanyl [patch] (FEN ta nil)
Brand name(s): DURAGESIC
GENERIC: not available
FAMILY: Opiate-containing Painkillers
Fentanyl is excreted in human milk. Because of the potential for adverse effects in nursing infants, you should not take this drug while nursing.
Fentanyl caused fetal death in animal studies. Because of the potential for serious adverse effects to the fetus, this drug should not be used by pregnant women.
Facts About This Drug:
Fentanyl is a synthetic narcotic that relieves pain. Most studies about fentanyl focus on the injectable form used during surgery. Fewer studies have been done on the transdermal (patch) form, and even fewer studies have been done on older people using fentanyl patches.
Fentanyl patches, which slowly release medication over three days, are used for are used for persistent, moderate to severe chronic pain that requires around-the-clock opioid administration for an extended period of time and cannot be managed by other means. Pain relief usually improves sleep. People with swallowing difficulties or poor veins benefit from the topical application. Others find the patch convenient. However, fentanyl is not a Band-Aid for mild or intermittent pain, and is not usually used until doses of oral morphine have become high and frequent. Using cut or damaged patches can cause a high dose of the drug to be released and absorbed, which can be fatal. The first dose of fentanyl is usually 25 micrograms (this refers to the number of micrograms released each hour). Doses must be estimated according to prior use of other analgesics. Older people usually need less fentanyl than younger people. It may take a few days until adequate pain relief is achieved. During the transition, other shorter-acting analgesics relieve breakthrough pain. One drawback of the patches is less flexibility in doses, which are currently limited to four sizes and their combinations. People who lose weight may need to have their dose lowered, since fentanyl is stored in fat tissue. Fentanyl should not be used on as-needed basis.
Fentanyl is not recommended for those weighing less than 110 pounds. Common adverse effects of fentanyl are nausea, vomiting, constipation, and skin irritation from the adhesive on the patch. Fentanyl patches are not recommended after surgery due to risk of severe respiratory problems. Like morphine, fentanyl is a controlled substance and could be habit-forming. The cost of fentanyl patches is more than short-acting oral morphine, similar to long-acting oral morphine, and usually less than injectable morphine, which involves costs for supplies and equipment.
In July of 2005, the FDA issued a Public Health Advisory and added extensive safety warnings to the professional product label of fentanyl in response to reports of death linked to the use of the fentanyl transdermal patch. The new warnings identify several important safety precautions, which are described below.
Fentanyl skin patches should not be used in the following situations:
in patients who have not previously been prescribed opioid painkillers
in the management of acute pain or in patients who require opioid pain killers only for a short period of time
in the management of post-operative pain, including use after out-patient or same-day surgeries
in the management of mild pain
in the management of intermittent pain
Fentanyl skin patches interact with a number of drugs that can increase the amount of fentanyl in the blood to dangerous levels. These drugs include ritonavir (KALETRA, NORVIR), ketoconazole (NIZORAL), itraconazole (SPORANOX), troleandomycin (TAO), clarithromycin (BIAXIN), nelfinavir (VIRACEPT), and nefazodone (SERZONE).
Damaged or cut fentanyl skin patches should not be used. Damage to the skin patch can lead to the rapid release of its contents and absorption of a potentially fatal dose of fentanyl.
A copy of the FDA-approved Medication Guide is available here (http://www.fda.gov/cder/drug/InfoSheets/patient/fentanylPIS.htm).
Before You Use This Drug:
Do not use if you have or have had:
Tell your doctor if you have or have had:
allergies to medications or adhesives
emphysema, asthma, or other lung problems
colitis or inflammatory bowel disease
alcohol or drug abuse
head injuries or brain tumor
kidney or liver problems
suicidal ideation or attempt
enlarged prostate or difficulty urinating
recent urinary tract surgery
pregnancy or are breast-feeding
not opioid tolerant
Tell your doctor about any other drugs you take, including aspirin, herbs, vitamins, and other nonprescription products.
When You Use This Drug:
Read the patient instructions carefully before using.
To avoid constipation, drink plenty of water or fluids. Eat fiber. Take a stool softener. If constipation develops, you may need a laxative or enema.
Do not use more than directed by your doctor; it may take 24 hours before effects are felt.
Until you know how you react to fentanyl, avoid driving or performing other activities requiring alertness, as fentanyl can cause drowsiness.
Avoid drinking alcohol, which adds to central nervous system (CNS) effects of fentanyl.
Until your dose of fentanyl stabilizes, you may need another short-acting pain reliever for breakthrough pain.
If you plan to have any surgery, including dental, tell your doctor that you take this drug.
Do not use heating pads, electric blankets, heated water beds, hot tubs, saunas, or heat lamps. These could cause fentanyl to be too rapidly absorbed, especially if devices slip onto the patch while you sleep.
You may feel dizzy when rising from a lying or sitting position. When getting out of bed, hang your legs over the side of the bed for a few minutes, then get up slowly. When getting up from a chair, stay beside the chair until you are sure that you are not dizzy.
If nausea develops, try lying down until it subsides.
You may wear fentanyl patches while bathing, showering, or swimming, but do not rub the patch vigorously or stay for a prolonged time in hot water. If the patch loosens or dislodges, contact your doctor.
If you sleep or nap near someone else, cover the area of the patch with clothing. Otherwise, the patch could transfer to the other person. This has caused children to receive overdoses.
How to Use This Drug:
If you miss a dose, take it as soon as possible, but skip it if it is almost time for the next dose. Do not take double doses.
Do not share your medication with others.
Take the drug at the same time(s) each day.
Prepare the site with water. Do not shave the site or use soap, alcohol, or lotions. Do not apply to areas that are burned, cut, or irritated. Clip hair if necessary.
Remove liner just before using. Take care not to touch the adhesive surface. Wash with clean water any area the medication unintentionally touches.
Do not use if seal is broken or patch is otherwise damaged or cut.
Apply entire patch to dry skin above the waist. Press firmly with palm of hand for at least 30 seconds, especially around the edges.
If applying more than one patch, do not let edges overlap or touch. Rotate site of application, preferably alternating sides of the body.
Change patch every three days, unless your doctor tells you to change at a different frequency.
Do not apply more than the prescribed dose.
Fold used patches in half with adhesive layer inside the fold. Flush down toilet or otherwise dispose of in secure manner.
Do not stop using abruptly. A gradual reduction prevents withdrawal symptoms. Even if you stop using fentanyl patches, some of the drug can remain in older people for a few days.
Store at room temperature. Do not expose to heat, moisture, or strong light. Keep out of reach of children.
Interactions with Other Drugs:
The following drugs are listed in the Evaluations of Drug Interactions 2003 as causing “highly clinically significant” or “clinically significant” interactions when used together with this drug. We have also included potentially serious interactions listed in the drug’s FDA-approved professional product labeling or package insert. New scientific techniques have allowed researchers to predict some drug interactions before they have been documented in people. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. The number of new drugs approved for marketing increases the chance of drug interactions, and new drug interactions are being identified with old drugs. Be vigilant. Make sure to tell your doctor and pharmacist the drugs you are taking and tell your doctor if you are taking any of these interacting drugs:
People who take monoamine oxidase inhibitors should be off these drugs for 14 days before starting fentanyl. These include: deprenyl, ELDEPRYL, furazolidone, FUROXONE, isocarboxazid, MARPLAN, MATULANE, NARDIL, PARNATE, phenelzine, procarbazine, selegiline, tranylcypromine.
Central nervous system (CNS) depressant drugs, including alcohol, antidepressants, antihistamines, antipsychotics, some blood pressure medications (reserpine, methyldopa, beta-blockers), motion sickness medications, muscle relaxants, narcotics sedatives, sleeping pills, and tranquilizers. Doses of fentanyl and any of these drugs may need to be lowered by 50%. If any of these drugs are discontinued while you use fentanyl, adjustments in doses may be required.
Other drugs that can interact with fentanyl are: carbamazepine, DILANTIN, EES, erythromycin, ketoconazole, MERIDIA, naltrexone, NIZORAL, NORVIR, phenytoin, REVIA, RIFADIN, rifampin, ritonavir, sibutramine, TEGRETOL.
Call your doctor immediately if you experience:
difficulty breathing (If you care for a person who uses fentanyl patches and their breathing slows while sleeping, try to waken them. If breathing does not improve once awake, call their doctor.)5
slow, fast, pounding, or irregular heartbeat
dizziness, incoordination, or fainting
fever with or without chills (your dose may be lowered temporarily)5
restlessness or nervousness
cold, red, swollen, or blistered skin with or without itching at patch
thickened or scaly skin
combative and/or suspicious thoughts
difficulty urinating (decreased frequency and/or volume)
mental or mood changes
any change in vision
Call your doctor if these symptoms continue:
nausea or vomiting
red or itchy skin, sweating, tingling or burning sensation
abdominal or stomach pain
Call your doctor if these symptoms continue after you stop taking this drug:
nervousness, restlessness, or irritability
nausea or vomiting
unusually enlarged pupils
shivering or trembling
fever, runny nose, or sneezing
loss of appetite
Ask your doctor which of these tests should be done periodically while you are taking this drug:
degree of sedation
In the end, while fentanyl is an effective pain reliever, it has been associated with some very serious side effects and its extremely high potency makes it a very dangerous drug when misused. An overdose of fentanyl can have deadly consequences in a matter of minutes.
As a result of the ongoing problems with the Fentanyl Transdermal System, especially with respect to accidental overdosing caused by manufacturing defects, there have been numerous successful lawsuits brought for injuries and deaths caused by these patches.
If you believe you or a relative has suffered a fentanyl-related injury or you believe a loved one died as a result of a reaction to or overdose of fentanyl, do not hesitate to contact the attorneys at Parker Waichman LLP at www.yourlawyer.com for a free consultation and review of the facts.